Análise das alterações citogenéticas e sua associação com características clínicas e evolução das crianças e adolescentes com leucemia mieloide aguda

Abstract

AML is rare in children, accounting for approximately 15-20% of cases of childhood leukemia. Chromosomal rearrangements can be observed in more than 70% of the cases, being recognized as an important prognostic factor. To date, there is little data on the disease and the survival of the children it affects in Brazil. Objective: To evaluate the association of cytogenetic changes with the clinical characteristics and evolution of children and adolescents with acute myeloid leukemia (AML). Patients and methods: A retrospective cohort study was performed. The study population consisted of 98 patients up to the age of 16 years, with diagnosis of AML, attended at the Hematology Service of Hospital of the Clinics - UFMG, from 2004 to 2015. Results: In the present study, 51% of the cases corresponded to female patients. The median age at diagnosis was 7,64 years and the median global leukocyte count at diagnosis was 10.780 / mm3. Regarding FAB classification, M3 subtypes (33 patients - 34% of cases) and M2 (21 patients - 21% of cases) predominated. Among the 80 patients for whom it was possible to analyze the karyotype, 63 (78,6%) had some chromosomal alteration, the most frequent being t (15; 17) (q22; q21). In relation to the classification of WHO-2008, of 86 patients, 45 (52%) were classified in the group with recurrent genetic abnormalities, 16 (18,6%) in the group with cytogenetic changes related to myelodysplasia, 19 (22%) in the group "AML without further specification" (SOE) and six patients (7%) had Down syndrome-related leukemia. The estimated overall survival (OS) at five years for the whole group was 49,7% (± 5.2%). The estimated probability of OS at 5 years for patients with normal karyotype was 56,6% (± 12,7%), from 81,0% (± 8,6%) for those with t (15; 17), of 71,4% (± 17,1%) for patients with t (8; 21), of 20,5% (± 12%) for patients with cytogenetic changes related to myelodysplasia and of 46,9% (± 13,4%) for the group with other abnormalities (p = 0,028). Regarding the classification of WHO 2008, in the univariate and multivariate analysis, patients with cytogenetic alterations related to myelodysplasia and those with non-specific AML presented an unfavorable prognosis when compared to patients in the "AML with recurrent genetic abnormalities" and "Down syndrome AML". In the multivariate analysis, the variables "WHO-2008 classification" and "leukocyte count at diagnosis <100.000 or 100.000 leukocytes / mm3" were included. Patients with AML with "cytogenetic changes related to myelodysplasia" presented a 2,97 times greater chance of death than patients with recurrent genetic abnormalities, considered the base category. Patients of the category without other specification (SOE), compared to the base category, presented 2,22 times more chance of death. Patients with AML associated with Down syndrome presented a death rate 0,58 times greater than the baseline category, but without statistical significance (p = 0,601).The effect of leucometry (above or below 100.000 / mm3) is not independent (p = 0,078) from the WHO-2008 classification, although there is a tendency to do so Conclusion: Despite the limitations of a relatively small retrospective study, the results corroborate the importance of cytogenetic changes as a prognostic factor for pediatric patients with AML